Adrenal insufficiency Flashcards
What are some causes of primary adrenal insufficiency?
- Addison’s disease
- Congenital adrenal hyperplasia (Not the same as bilateral adrenal hyperplasia)
- APS type I/II
- Adrenalitis (TB, HIV, CMV, Syphilis)
- Haemorrhage
- Genetic disorders
- Adrenal TB
- Adrenal malignancy
- Drugs
What are some drugs that can cause primary adrenal insufficiency?
Anti-coagulants
Adrenal enzyme inhibitors (E.g. ketoconazole, phenobarbital)
What are some genetic conditions that can lead to primary adrenal insufficiency?
Congenital adrenal hyperplasia (Commonest cause in children)
Adrenoleukodystrophy
What is Addison’s disease?
An autoimmune condition affecting the adrenal cortex and is the most common cause of primary adrenal insufficiency
What are some other autoimmune conditions associated with Addison’s disease?
- Type I diabetes
- Autoimmune thyroid disease
- Pernicious anaemia
What occurs in Addison’s disease?
Autoimmune destruction of the adrenal cortex, with 90% of cases involving full destruction before symptoms occur
How will Addison’s disease present?
Skin pigmentation (Bronzing)
Salt craving
Anorexia
Lethargy/Fatigue
Dizziness
Low BP
Abdominal pain
Vomiting and diarrhoea
How does Addison’s disease cause hyperpigmentation?
Low cortisol leads to a build up of ACTH
ACTH build up begins to act as MSH (Melanocyte stimulating hormone), causing hyperpigmentation
What are some autoantibodies found in Addison’s disease?
- Adrenal cortex antibodies
- 21-Hydroxylase antibodies
What is an adrenocortical carcinoma?
Very rare malignancy of the adrenal cortex
Who is most at risk of adrenocortical carcinoma?
Adults
Young people with Li-Fraumeni syndrome
Equal sex incidence
Describe the histology of an adrenocortcial carcinoma
- Large size (>50g, often >20cm)
- Haemorrhage and necrosis
- Frequent mitosis, atypical mitoses
- Lack of clear cells
- Capsular or vascular invasion
Where will adrenocortical carcinoma locally invade?
Retroperitoneum
Kidneys
Where does adrenocortical carcinoma metastasise to?
Liver
Lung
Bone
Regional lymph nodes
How do adrenocortical carcinomas present?
- Hormonal changes
- Abdominal mass
- Fever (If necrosis)
What investigations are required in adrenocortcial carcinoma?
- CT
- MRI
- Biopsy
How is adrenocortcial carcinoma managed?
Resection with adjuvant therapy (If not metastatic)
What are some causes of secondary adrenal insufficiency?
- Pituitary tumours
- Surgery/Radiation
- Infiltrative infection
- Pituitary apoplexy
- Sheehan’s syndrome
- Lack of ACTH stimulation
- Iatrogenic (Excess exogenous steroid)
- Pituitary/hypothalamic disorders
What causes tertiary adrenal insufficiency?
Conditions affecting the hypothalamus
What is the most common cause of secondary adrenal insufficiency?
Sudden cessation of exogenous steroid use
After how long of steroid therapy can dosage not be suddenly stopped?
3 weeks
How much cortisol does the body produce per day?
7mg
How does sudden cessation of exogenous steroid usage cause adrenal insufficiency?
Exogenous steroids increase blood ‘cortisol’ levels, therefore depressing the HPA axis and decreasing ACTH production
If this is stopped, ATCH production will still be low and so adrenal crisis may occur
What are some presentations of secondary adrenal insufficiency?
- Anorexia/Weight loss
- Fatigue/Lethargy
- Dizziness
- Low BP
- Abdominal pain
- Vomiting and diarrhoea
- Pallor
What are some tests required in diagnosis of adrenal insufficiency?
- Biochemistry
- Short synacthen test
- Long synacthen test
- ACTH levels
- Renin/aldosterone levels
- Adrenal autoantibodies
- Imaging
What is the function of short synacthen test?
Tests for adrenal insufficiency
What is the function of a long synacthen test?
Determines if adrenal insufficiency is primary or secondary
What is involved in a short synacthen test?
The short synacthen test involves measuring plasma corticol before and 30 minutes after IV/IM ACTH injection
Normal baseline >250nmol/L
Normal post ACTH >550nmol/L
How are ACTH levels affected in primary adrenal insufficiency?
Highly increased
How will renin be affected in primary adrenal insufficiency?
Highly increased
How will primary adrenal insufficiency affect aldosterone levels?
Decreased
How is adrenal insufficiency managed?
- Hydrocortisone (Cortisol replacement)
- Fludrocortisone (Aldosterone replacement)
- Education
What is required in fludrocortisone therapy?
Careful monitoring of BP and K+
What education is required in adrenal insufficiency management?
- “Sick day rules”
- Cannot stop suddenly
- Need to wear identification
What are the steroid sick day rules?
- Moderate intercurrent illness (e.g. fever, infection requiring antibiotics) or local anaesthetic ⇒ Double daily steroid dose
- Severe intercurrent illness (e.g. persistent vomiting from GI illness), colonoscopy, acute trauma or surgery ⇒ HC 100mg IV followed by continuous 200mg 24hour IV HC
Patients must be supplied with education on how to self administer 100mg IM hydrocortisone
What is an adrenal crisis?
Acute, severe glucocorticoid deficiency caused by either stress in a patient with underlying adrenal insufficiency or sudden discontinuation of glucocorticoids after prolonged glucocorticoid therapy
What are some symptoms of adrenal crisis?
- Abdominal pain
- Confusion
- Loss of consciousness
- Coma
- Dehydration
- Dizziness or lightheadedness
- Fatigue, severe weakness
- Headache
- High fever
- Loss of appetite
How is adrenal crisis managed?
- 0.9% NaCl saline fluids
- 100mg IV hydrocortisone
- Treatment of underlying condition
- Close cardiac monitoring
What is congenital adrenal hyperplasia?
Inherited group of disorders characterised by a deficiency in one of the enzymes necessary for cortisol synthesis
What is the most common enzyme deficiency in congenital adrenal hyperplasia?
Autosomal recessive 21⍺-hydroxylase deficiency
Describe the pathophysiology of congenital adrenal hyperplasia
- 21⍺-hydroxylase deficiency prevents the production of aldosterone and cortisol
- Increased volume of precursors will be diverted into the androgen pathway → increased testosterone and dihydrotesterone
- Reduced cortisol stimulates ACTH release and cortical hyperplasia
What are the 2 sub-types of congenital adrenal hyperplasia?
Classic CAH (Early-onset)
Non-classic CAH (Late-onset - Partial deficiency)
When will classic CAH present?
Birth or shortly afterwards
When will non-classic CAH present?
Adolescence or adulthood
How will classic CAH present?
- Genital ambiguity (virilisation) in females
- Adrenal failure:
- Collapse
- Hypotension
- Hypoglycaemia
- Poor weight gain
- Biochemical patten of Addison’s disease
How will non-classic CAH present?
- Precocius puberty
- Hirsutism
- Acne
- Oligomenorrhoea, infertility or sub-fertility
What investigations are required in congenital adrenal hyperplasia?
- Basal (or stimulated) 17-OH progesterone
- Genetic analysis
How is CAH managed in children?
- Glucocorticoid replacement
- Mineralocorticoid replacement in some
- Surgical correction
- Achieve maximal growth
How is CAH managed in adults?
- Glucocorticoid replacement, avoiding steroid over-replacement
- Control androgen excess
- Restore fertility
